The purpose of this study is to evaluate the mechanisms of action of growth-promoting polypeptide hormones. The effects of epidermal growth factor (EGF) were evaluated by scanning electron microscopy in human and murine epithelial cells and were found to be reversible, dose-dependent, and dependent on the number of surface receptors. Plasma membrane mobility, macropinocytosis, and cell proliferation were enhanced. Comparative studies revealed that epithelial cells of different origin respond differently to EGF, and that membrane ruffling followed by pinocytosis was the prevalent, early specific morphologic response. This response was clearly defined in murine epithelial cells, strain MMC-E, thus making these cells the preferred model for such studies.